Childhood-onset Obsessive-compulsive disorder (OCD) and tic disorders appear to arise, in some cases, as sequelae of common childhood infections, including Group A beta-hemolytic streptococcal (GABHS) infections. Children whose symptoms begin or exacerbate following GABHS infections may belong to a subgroup of neuropsychiatric disorders identified by the acronym PANDAS (for Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal infections). The subgroup shares several common clinical characteristics in common, and also may share a common pathophysiology for their symptoms. Investigations of the nature and treatment of this novel subgroup are ongoing. For example, data from a recently completed community study demonstrated that transient motor tics are common among elementary school students, with a monthly prevalence rate of 3% - 10%. Further, tics are more frequently present during months when streptococcal infections are increased (November through February) than during the spring months(March through June). During this reporting period, additional experience has been gained in the use of long-term antibiotic administration (prophylaxis) to prevent post-streptococcal neuropsychiatric symptom exacerbations. In addition, an ongoing study being conducted in collaboration with the University of Florida - Gainesville, is examining the relationship between symptom onset and clinical course. Children with recent-onset OCD are enrolled in the trial and followed prospectively for up to two years to determine whether or not acute, dramatic onset of symptoms will predict an episodic course. Further, associations between symptom exacerbation and streptococcal infections are being tracked to determine whether or not membership in the PANDAS subgroup can be predicted at initial presentation. In addition, a collaboration with Drs. Madeleine Cunningham (Univ. Oklahoma) and Christina Kirvan (UC-Davis) is examining the relationship between cross-reactive antineuronal antibodies and symptoms in the PANDAS subgroup, and children with Sydenham chorea. A paper published in Nature-Medicine (July 2003) described the presence of antibodies reactive with glycoproteins present on both the streptococcal bacteria cell wall, and neuronal tissue. Acute titers were significantly higher than convalescent titers among serum samples obtained from patients with Sydenham chorea. A replication of these findings, and extension to the PANDAS subgroup is ongoing.